A Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation

Alzheimer Disease Clinical Trial

— MINDFuL  

Official title:

A Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05318976
• Other study ID #: XPro1595-AD-02
• Status: Recruiting
• Phase: Phase 2
• Start date: February 28, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Inmune Bio, Inc.
• Contact: INmune Bio
• Phone: (858)964-3720
• Email: trials[@]inmunebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this Phase 2 Alzheimer's study is to determine whether 1.0 mg/kg XPro1595 confers a benefit on cognition, function, and biomarkers of white matter and to further evaluate safety and tolerability. The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with early ADi.

Description:

This trial is a randomized clinical study using XPro1595 to treat patients with Early Alzheimer's Disease with biomarkers of inflammation (ADi). Early ADi patients are defined as patients with Mild Alzheimer's Disease or Mild Cognitive Impairment with a biomarker of inflammation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 201
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

To be eligible for study entry, patients must satisfy all of the following criteria:

• Adult patients 50 years to = 85 years of age at the time of consent;

• Meets the diagnostic criteria of MCI of probable Alzheimer's disease (Jack et al. 2018; NIAAA) or mild dementia as clinically described in McKhann, (2011) and corresponding to stages 3 or 4 of the revised AD staging system (Jack, 2018);

• Either currently or previously (in pre-AD condition) literate and capable of reading, writing, and communicating effectively with others;

• Residence in an assisted living is allowed as is personal assistances provided in the home, however at time of enrollment participant must be able to perform most ADL with minimal assistance, and participant must be permitted sufficient independence to allow assessment of change in ADL;

• Has a study partner for the duration of the trial who either lives in the same household or interacts with the patient at least 4 hours per day and on at least 4 days per week, who is knowledgeable about the patient's daytime and night-time behaviors and who can be available to attend all clinic visits in person at which caregiver assessments are performed.

Exclusion Criteria:

Patients will be excluded from the study if 1 or more of the following criteria are applicable:

• Have any contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in-skull and cardiac devices other than those approved as safe for use in MRI scanners);

• Receives considerable help to carry out basic ADL living either in the home or as a resident in a nursing home or similar facility;

• Lifetime history of a major psychiatric disorder including schizophrenia and bipolar disorder. Major depressive disorder that has resulted in 2 or more hospitalizations in a lifetime. Major depressive episode during the past 5 years that is judged by the clinical team unlikely to have been part of Alzheimer's prodrome. History of suicidality. History of substance abuse within 12 months; use of cannabis or cannabis products within 6 months of consent;

• Enrolled in another clinical trial where patients receive treatment with an investigational drug or treatment device or have received treatment on another AD clinical trial within the last 60 days from Day 1;

• A prior organ or stem cell transplant;

• Seated blood pressure of = 165/105 mmHg at Screening.

Related Conditions & MeSH terms

• Alzheimer Disease
• Brain Diseases
• Central Nervous System Diseases
• Cognitive Dysfunction
• Dementia
• Inflammation
• Mental Disorders
• Mild Cognitive Impairment
• Nervous System Diseases
• Neurocognitive Disorders
• Neurodegenerative Diseases
• Tauopathies

Intervention

Drug:
• XPro1595
XPro1595 will be delivered by subcutaneous injection once a week
• Placebo
Placebo will be delivered by subcutaneous injection once a week

Locations

Country	Name	City	State
Australia	INmune Bio Investigational Site	Adelaide	South Australia
Australia	INmune Bio Investigational Site	Box Hill	Victoria
Australia	INmune Bio Investigational Site	Carlton	Victoria
Australia	INmune Bio Investigational Site	Darlinghurst	New South Wales
Australia	INmune Bio Investigational Site	Ivanhoe	Victoria
Australia	INmune Bio Investigational Site	Macquarie Park	New South Wales
Australia	INmune Bio Investigational Site	Parkville	Victoria
Australia	INmune Bio Investigational Site	Perth	Western Australia
Canada	INmune Bio Investigational Site	Ottawa	Ontario
Canada	INmune Bio Investigational Site	Toronto	Ontario
Germany	INmune Bio Investigational Site	Berlin
Poland	INmune Bio Investigational Site	Bialystok
United Kingdom	INmune Bio Investigational Site	Birmingham
United Kingdom	INmune Bio Investigational Site	Bristol
United Kingdom	INmune Bio Investigational Site	Guildford
United Kingdom	INmune Bio Investigational Site	London
United Kingdom	INmune Bio Investigational Site	Motherwell
United Kingdom	INmune Bio Investigational Site	Plymouth
United Kingdom	INmune Bio Investigational Site	Winchester

Sponsors (1)

Lead Sponsor	Collaborator
Inmune Bio, Inc.

Countries where clinical trial is conducted

Australia,  Canada,  Germany,  Poland,  United Kingdom, 

References & Publications (4)

Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006 May 17;295(19):2275-85. doi: 10.1001/jama.295.19.2275. Erratum In: JAMA. 2006 Jun 7;295(21):2482. — View Citation

Chance SA, Clover L, Cousijn H, Currah L, Pettingill R, Esiri MM. Microanatomical correlates of cognitive ability and decline: normal ageing, MCI, and Alzheimer's disease. Cereb Cortex. 2011 Aug;21(8):1870-8. doi: 10.1093/cercor/bhq264. Epub 2011 Jan 14. — View Citation

Chou RC, Kane M, Ghimire S, Gautam S, Gui J. Treatment for Rheumatoid Arthritis and Risk of Alzheimer's Disease: A Nested Case-Control Analysis. CNS Drugs. 2016 Nov;30(11):1111-1120. doi: 10.1007/s40263-016-0374-z. — View Citation

Clark I, Atwood C, Bowen R, Paz-Filho G, Vissel B. Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales. Pharmacol Rev. 2012 Oct;64(4):1004-26. doi: 10.1124/pr.112.005850. Epub 2012 Sep 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Goal Attainment Scale (GAS)	Change in individual goals based on the Goal Attainment Scale (GAS); The achievement of each goal is rated on a 5-point attainment scale (-2, -1, 0, +1, +2) to allow standardized scoring of personalized outcomes. A participant's overall goal attainment is quantified using a formula that takes into account the number of goals that have been set, and the extent to which they are correlated with each other. For each identified goal area, the caregiver will be asked to give a detailed description of the patient's current (baseline) status and goal status, which will be recorded at the -1 and 0 levels on the 5-point scale, respectively. The remaining levels of the scale will then be set: somewhat better than the goal (+1), much better than the goal (+2), and much worse than the goal (-2).; To evaluate the effect of XPro1595 compared with placebo on goal attainment scores	24 Weeks
Primary	Change in Early and Mild Alzheimer's Cognitive Composite (EMACC)	Change in the Early and Mild Alzheimer's cognitive composite (EMACC) from Baseline to Week 24 in the following assessments: International Shopping List Test-Immediate recall (Word List learning Test); Digit Span Forward and Backward; Category Fluency Test (DKEFS); Letter Fluency Test (DKEFS); Trail Making Test Parts A and B; Digit Symbol Coding Test; To assess the efficacy of XPro1595 compared with placebo on cognitive performance in patients with mild AD	24 Weeks
Secondary	Change in Clinical Dementia Rating (CDR)	Change from Baseline to Week 24 in Clinical Dementia Rating Scale (CDR); The CDR scale is a clinician-rated dementia staging system that tracks the progression of cognitive impairment in 6 categories (memory, orientation, judgement, and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5-point scale in which None = 0, Questionable = 0.5, Mild = 1, Moderate = 2, and Severe = 3. The global CDR score is established by clinical scoring rules and has values of 0 (no dementia), 0.5, (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). The Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment.; To assess the effect of XPro1595 compared with placebo on cognition and global function in patients with mild AD	24 Weeks
Secondary	Change in apparent fiber density (AFD)	Change from Baseline to Week 24 in apparent fiber density (AFD); To assess the efficacy of XPro1595 compared with placebo on axonal integrity in patients with mild AD	24 Weeks
Secondary	Change in Everyday Cognition (E-Cog)	Change from Baseline to Week 24 in Everyday Cognition (E-Cog); To evaluate the effect of XPro1595 compared with placebo on E-Cog	24 Weeks
Secondary	Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)	Change from Baseline to Week 24 in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL); To assess the effect of XPro1595 compared with placebo on ADL in patients with mild AD.	24 Weeks
Secondary	Change in myelin content	Change from Baseline to Week 24 in free-water-corrected tissue Radial diffusivity and 1 of the following i) MRI-specific myelin contrast: ii) a magnetization transfer ratio (MTR) iii) an inhomogeneous magnetization transfer (MT) or iv) an myelin water fraction (MWF) map; To assess the efficacy of XPro1595 compared with placebo on myelin in patients with mild AD.	24 Weeks
Secondary	Change in non-cognitive behavioral symptoms	Change from Baseline to Week 24 in (Neuropsychiatric Inventory [NPI] caregiver items); To assess the effect of XPro1595 compared with placebo on noncognitive behavioral symptoms in patients with mild AD	24 Weeks
Secondary	Change in gray matter integrity	Change from Baseline to Week 24 in Cortical Disarray Measurement (CDM®); To assess the efficacy of XPro1595 compared with placebo on gray matter integrity in patients with mild AD	24 Weeks
Secondary	Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)	Number of participants with a reduction in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration amyloid) from Baseline to Week 24.; To assess the efficacy of XPro1595 compared with placebo on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid).	24 Weeks
Secondary	Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)	Change from Baseline to Week 24 in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau); To assess the efficacy of XPro1595 compared with placebo on blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)	24 Weeks
Secondary	Change in brain structure neurodegeneration	Changes from Baseline to Week 24 in volumetric magnetic resonance imaging (MRI); To assess the efficacy of XPro1595 compared with placebo on brain structure neurodegeneration	24 Weeks
Secondary	Number of participants who experience adverse events and serious adverse events	Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram findings and other safety assessments will be recorded as adverse events if the findings meet the defined criteria for adverse events.	Baseline up to 28 days post last dose

External Links

•   Alzheimer's Association annual report releasing statistics regarding Alzheimer's disease